Significant recent advances have been made in strategies for managing ST-segment elevation myocardial infarction (STEMI). Based on new findings, the American College of Cardiology (ACC) and the American Heart Association (AHA) have updated their guidelines for acute myocardial infarction (MI) with newer recommendations for STEMI management. Many of these recommendations focus on antithrombotic agents, with a movement toward lower doses of long-term aspirin and lower doses of unfractionated heparin (UFH). Studies have also been completed on the use of enoxaparin and fondaparinux as potential alternatives to heparin, and clinical trial data support the early use of glycoprotein IIb/IIIa inhibitors (along with aspirin, UFH, and clopidogrel) in patients undergoing primary percutaneous coronary intervention for acute STEMI. Clopidogrel has also been shown to improve angiographic and clinical outcomes in patients with STEMI who are undergoing thrombolysis or being treated medically. The new ACC/AHA recommendations support clopidogrel pretreatment and long-term therapy.